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Clinical Effects of Cherry and Blueberry Juice on Cardiometabolic Risk Factors and Sleep in Healthy Adults; A Trial with Multiple Issues

Date 03-31-2023
HC# 082252-709
Montmorency Tart Cherries (Prunus cerasus, Rosaceae)
Blueberries (Vaccinium sp., Ericaceae)
Cardiometabolic Disease

Sinclair J, Bottoms L, Dillon S, Allan R, Shadwell G, Butters B. Effects of Montmorency tart cherry and blueberry juice on cardiometabolic and other health-related outcomes: a three-arm placebo randomized controlled trial. Int J Environ Res Public Health. April 2022;19(9):5317. doi:10.3390/ijerph19095317.

Cardiometabolic diseases are a major cause of global mortality and healthcare expenditure. These diet and lifestyle-related diseases include hypertension, insulin resistance, atherogenic dyslipidemia, low high-density lipoproteins, high triglycerides, high adiposity, high body mass index, large waist-to-hip ratio, and poor glucose regulation. Although pharmaceutical interventions are available, efficacy and cost-effectiveness remain ambiguous. Many medications also have negative side effects. Dietary intervention is known to be the most effective natural approach to treating cardiometabolic disease; however, a variety of reasons can cause a person not to be compliant. This has led to evaluating dietary supplementation and its effects on the body.

Anthocyanins give dark-colored fruits their pigment and may significantly improve cardiometabolic health. These bioactive polyphenolic compounds, and their derivatives, have been associated with anti-inflammatory, antioxidant, and fat oxidation properties. Two fruits with high anthocyanin concentrations are Montmorency tart cherries (Prunus cerasus, Rosaceae) and blueberries (Vaccinium sp., Ericaceae). Studies exploring the efficacy of anthocyanin-rich juices have yielded mixed results indicating the need for further studies. Thus, the authors conducted a 20-day parallel, single-blind randomized placebo-controlled trial with Montmorency tart cherry juice and blueberry juice supplementation on cardiometabolic and other health-related indices compared to placebo in healthy participants.

The trial occurred at the University of Central Lancashire, United Kingdom (UK). While it was not stated when it took place, the listing notes the study duration running from January 2020 through February 2022. The inclusion criteria included men and women between the ages of 18 and 65 who were non-smokers, had a body mass index < 30, and were able to give informed consent. Exclusion criteria included participants who had diabetes or any other metabolic or uncontrolled hypertensive conditions, had an allergy to cherries or blueberries, consumed blueberries or cherries regularly, were pregnant, or were taking regular medication or antioxidant supplements.

Participants were split into the cherry, blueberry, and placebo groups. The cherries (320 mg anthocyanins) and blueberries (387 mg anthocyanins) were obtained from ActiveEdgeTM (Wintney, UK), and 30 mL were added to 100 mL of water and consumed twice daily. The placebo was un-flavored maltodextrin carbohydrates (MyProteinTM; Chesire, UK) that were added to water. Red and black book coloring or red, blue, and black food coloring was added to make the placebo appear like the blueberry or cherry supplement. Flavdrops (MyProtein) were also added to match the taste.

Systolic and diastolic blood pressure, anthropometric, energy expenditure and substrate oxidation, hematological, resting heart rate, psychological wellbeing, and sleep efficacy indices were obtained at baseline and after 20 days. Testing took place in the morning after a 10 hr fasted state. Participants could not exercise strenuously, consume alcohol or nutritional supplements for 24 hr before testing, and were asked not to consume caffeine for 12 hr prior to data collection. Anthropometric data included mass, stature, body mass index, body composition, percentage body fat, fat mass, waist circumference, and hip circumference. Energy expenditure included obtaining respiratory gases and resting fat and carbohydrate oxidation rates, resting metabolic rate, and carbohydrate-oxidation and fat-oxidation rates were calculated during resting and moderate-intensity physical activity. Blood samples included triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose levels. General sleep quality was obtained using the Pittsburgh sleep quality index, daytime sleepiness was obtained using the Epworth Sleepiness Scale, and symptoms of insomnia were analyzed using the Insomnia Severity Index. Psychological wellbeing was analyzed using the COOP/WONCA questionnaire, the Beck Depression Inventory was used to record depressive symptoms, and the State Trait Anxiety Inventory to record state/trait anxiety.

Of the 44 participants enrolled in the study, 24 were male and 20 were female. There were 15, 14, and 15 participants in the placebo, cherry, and blueberry groups, respectively. There were no significant differences between groups for age, mass, stature, body mass index, or sex. Of the 44 participants, 23 were able to identify the supplement they were given, and the chi-squared test indicated this was not significant.

There was no significant difference in energy expenditure and substrate oxidation parameters. The blueberry group had a significant improvement in total cholesterol (P = 0.009) and LDL (P = 0.020) compared to placebo. Compared to blueberry, both placebo (P = 0.003) and cherry (P = 0.012) had lower glucose, and hemoglobin was reduced in the placebo group compared to the blueberry group. Total cholesterol was reduced for 80%, 86.7%, and 40% of participants in the cherry, blueberry, and placebo groups, respectively. LDL was reduced for 60%, 86.7%, and 33.3% of participants in the cherry, blueberry, and placebo groups, respectively. Triglycerides were reduced for 80%, 73.3%, and 40% of participants in the cherry, blueberry, and placebo groups, respectively. There were no significant differences in blood pressure or resting heart rate. The blueberry group saw a reduction in Beck Depression Inventory (P = 0.041), COOP WONCA (P = 0.019), state (P = 0.018), and trait anxiety scores (P = 0.023) compared to placebo. Trait anxiety score was significantly reduced in the blueberry group compared to cherry (P = 0.038). There was an adverse event reported in the cherry group only.

The authors conclude that cherry and blueberry juice did not improve systolic blood pressure; however, cherry and blueberry juice did improve blood lipid concentrations and psychological wellbeing indices. Limitations include using the manufacturer's anthocyanin, energy, and sugar reported content without third-party verification; lack of mechanistic bases for the improvement in cardiometabolic and psychological wellbeing indices; and not recording physical activity of each participant and anthocyanin intake before the study. More research is needed to understand the long-term effects of blueberry and cherry juice on cardiometabolic risk factors, sleep, and overall health. The authors declare no conflict of interest.

—Dani Hoots

Peer Reviewer Comments

The primary outcomes were improvement in systolic blood pressure for each treatment group compared to placebo, and there were no differences between the two treatments on how they performed compared to the placebo. However, there was no mention of the study being powered to assure that the sample size was adequate to observe these outcomes.

Dietary protein content varied among the three per 30mL: tart cherry had 18 g; blueberry had 22 g, and the placebo had 0 g. It is not clear why the authors did not try to match the placebo closer to the treatments.

The baseline blood pressure values were not statistically different among the groups, and each group had normal blood pressure based on systolic and diastolic readings.

The primary outcome was to observe a significant improvement in systolic blood pressure compared to placebo group, and this did not occur. It is unlikely that normal systolic reading would change in healthy, normal weight individuals with normal systolic readings. There was no difference between the two treatments’ effect on systolic blood pressure improvement compared to placebo, which was also a primary objective. The primary outcome of improving systolic blood pressure was buried in the manuscript; it is customary to display the results of the primary outcomes first, but the blood pressure changes appeared in Table 6).

There seemed to be no point to conducting this seemingly expensive study. Healthy, normal weight indviudals with normal sytolic blood pressure readings are unlikely to experience any improvement. It is possible that in order to make a structure/function claim on the tart cherry or blueberry product, a study would need to be conducted in healthy individuals. Such a claim would be something liks this: helps maintain healthy systolic blood pressure readings in healthy individuals with normal blood pressure.